Seasonal patterns for manic episodes have been reported.1–5 However, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes the specifier “with seasonal pattern” only for depression.6 Thus, patients cannot be classified as having “seasonal” affective disorder if their manic episodes occur in a particular season but they do not have seasonal depression.7 Descriptions of seasonal mania date back to the era of Hippocrates, who believed melancholia was attributed to the imbalance of four different humors (black bile, yellow bile, blood, phlegm), which were affected by environmental and seasonal changes.8 Pinel elegantly described the seasonality of manic attacks in “A Treatise on Insanity,” in which he noted that “it is curious to trace the effects of solar influence on the return of maniacal paroxysms. They generally begin immediately after the summer solstice, are continued with more or less violence during the heat of summer, and commonly terminate towards the decline of autumn… Maniacs of all descriptions are subject to a kind of effervescence or tumultuous agitation, upon the approach of very stormy warm weather.”9 In contrast, Kraepelin unified the diagnosis of melancholia and mania into the concept of a single disease with different presentations, with melancholia occurring more often during the autumn and winter and mania more often during the spring and summer.8,10 These observations are still relevant for the current practice of psychiatry because they represent the natural course of bipolar disorder without the influence of modern medications such as mood stabilizers, antipsychotics, and antidepressants. Because of the devastating effects of mania and depression, it would be very advantageous if patterns of recurrence could be identified so that early interventions could be undertaken to try to prevent or reduce the detrimental effects of repeated mood episodes.
Seasonal patterns of manic episodes in spring and summer have been extensively documented in the literature. However, some studies did not find any significant seasonal patterns for mania. Given the discrepancies in these reports, it is important to examine the extent of the evidence for seasonal mania in bipolar disorder. If significant occurrences of seasonal mania have been documented, some type of early intervention may help prevent recurrences or ameliorate their detrimental effects.
Strong evidence indicates that seasonal changes affect mood and behavior across species. For example, certain behaviors in animals, such as hibernation, breeding, and migration, have obvious seasonal patterns. The impact of seasonal changes on human activities and mood is not as obvious, especially in modern society. Nevertheless, seasonal affective disorder (SAD) is a salient example of the dramatic impact of seasons on human mental health.6 Most patients with seasonal affective disorder complain of fatigue, tend to crave sugar, and overeat and oversleep in fall and winter, while they experience increased energy and activation in spring and summer.11 Numerous research studies have also documented seasonal patterns in some patients with bipolar disorder. In order to take proactive measures to prevent manic relapse in certain seasons, it is important to understand why seasons have such an important impact on mental health.
The objectives of this review article were to (1) summarize the evidence for the seasonal occurrence of mania, (2) summarize the evidence for the non-seasonal occurrence of mania, and (3) explore the mechanisms that may account for seasonal mania.
The PubMed database was searched using the key word “seasonal mania” and 197 papers published between 1990 and 2011 were identified. Only original research studies published in English were used for this review. Of the 174 original research papers, the majority of the studies involved SAD, while only 29 dealt with seasonal mania. We also reviewed proposed mechanisms for the seasonality of mania and the link between melatonin/circadian rhythm and mania.
Among the 29 original research studies we examined, 23 showed a seasonal pattern for manic episodes (Table 1) and 6 did not show a clear seasonal pattern (Table 2). Most of the studies used hospital admission data to perform a retrospective analysis of the pattern of manic episodes. The studies showing a seasonal pattern for manic episodes included tropical and subtropical areas13–15,22,26 and temperate regions, including the United States, Canada, the United Kingdom, Russia, and Norway. Based on the reports from Table 1, mania usually peaks in temperate regions around the spring and summer seasons. These conclusions are based on hospital admission records, violence on inpatient units, and suicidality. The estimated prevalence of seasonal mania was around 15% in patients with bipolar disorder.2,28
Using hospital admission records to analyze the seasonal pattern of mania has many advantages. They include large sample size, long-term data collection, broad geographic areas (convenient for data collection), different ethnic groups and nationalities, and low cost. As a result, the findings are more representative of the true pattern of manic episode occurrence, especially for severe cases of manic episodes. However, there are some limitations to this methodology, including variations in diagnosis, variable admission criteria over a long period of time, and broad geographic areas (data may not be consistent in quality). In addition, there might also be a lag between first occurrence of mania and admissions.
In the studies that did not find any significant seasonal patterns for manic episodes, the populations came from both temperate and tropical (e.g., India) regions. Interestingly, among the 6 studies that did not find significant seasonal patterns for mania, 3 involved outpatients and used patient self-reports on mood changes to assess the seasonality of manic episodes.31,32,35 It is expected that outpatients with bipolar disorder generally have less severe symptoms, but many patients with bipolar disorder underestimate the severity of their manic symptoms.26 As a result, the approaches used in these studies might not represent treatment for the most severe form of bipolar illness in patients during their manic episodes. Although the study done by Partonen and Lönnqvist used admission data to assess the seasonality of manic episodes,34 there was a deficiency in the study design, which specifically used schizophrenia as a reference and assumed that occurrences of schizophrenia did not have seasonality. However, a study by Hare and Walter found that this assumption was not true; in that study, they found that both mania and schizophrenia had significant seasonality, with both peaking in summer.37 Hence, only two studies that used hospital admission data to assess the seasonal pattern of mania (Whitney et al. 199933 and Jain et al. 199236) did not find any significant seasonality., Although the Whitney et al. study, which used hospital admission records in a 75-year study in the Ontario Provincial Psychiatric Hospital,33 did not find any significant seasonal patterns for mania, they did find that mixed episodes peaked around summer.
The discrepancies between the evidence in Tables 1 and 2 are apparent, given the fact that mania occurs in a heterogeneous group of disorders (e.g., bipolar disorder, medication- or substance-induced mood disorders, in association with some general medical conditions), and presentations vary even in the same individual. In addition, criteria for admission and diagnosis vary among countries, regions, and institutions. For patients with a clear seasonal pattern of manic episodes, it would be interesting to know if medication adjustments may be able to prevent relapses during patients’ peak seasons. Unfortunately, we did not find any research studies on the effectiveness of adjusting the dosage of mood stabilizers to prevent the occurrence of seasonal manic episodes. We did locate one case report concerning medication adjustment38 and one case report showing that timing ECT prior to seasonal manic episodes successfully prevented seasonal manic relapse in one patient.39
How Is Season Linked to Mood?
One hypothesis posits that circadian rhythm plays a critical role in mania. The suprachiasmatic nucleus (SCN), located in the anterior hypothalamus, is responsible for the circadian rhythm (the master clock). The SCN receives input from the retina, and the circadian pituitary-adrenal rhythm is adjusted based on that input, under extensive modulation by the serotonergic neurons of the raphe nuclei. The first evidence indicating that the SCN was the biological master clock came from a study in rats, in which the SCN was lesioned. These rats lost their circadian rhythm for drinking activities.40 In addition, transplantation of cultured SCN cells into SCN-lesioned rats was able to restore their rhythmic activities.41 The effective functioning of the SCN neurons appears to be coordinated by gamma-aminobutyric acid (GABA), the predominant neurotransmitter in SCN.42 In humans, light-dark signals are transmitted to the SCN via the retinohypothalamic tract (RHT) with glutamate as the major neurotransmitter, while other neurotransmitters, such as substance P, adenylate cyclase activating peptide, and serotonergic neurons from the raphe nuclei are also involved.43,44 The activities of the SCN are also regulated by neurohormones, among which melatonin is the most important.45 Although the output pathways from the SCN are not very clear, evidence indicates that the GABA- containing axonal terminals from the SCN to paraventricular nuclei regulate melatonin synthesis in the pineal gland.46
Circadian Rhythm Disturbances in Bipolar Disorder
Insomnia is often a precursor or precipitant of mania/hypomania in patients with bipolar disorder. Therefore maintaining regular sleep-wake cycles is critical to the stability of patients with bipolar illness.47,48 It has been hypothesized that patients with bipolar disorder are genetically more sensitive to light, and that bright light in early morning will phase advance their sleep clock so that it becomes out of synchrony with other physiological rhythms, such as cortisol secretion and body temperature.49,50 Hence, if the patient’s sleep-wake cycle is advanced and thus out of synchronization with other circadian rhythms, this may trigger manic or hypomanic episodes. This hypothesis is consistent with the clinical presentations of many patients who wake up very early during manic episodes.
Mood Stabilizers and the Circadian Rhythm
Lithium is effective in reducing cycling in bipolar and recurrent unipolar depression. This reduction in cycling is neither immediate nor is it immediately lost upon discontinuation of treatment. Lithium has been found to modify the period and phase of circadian rhythms in species ranging from unicellular organisms to insects, mice, and humans.51–53 Lithium also lengthens the free-running circadian period across species, from single cells to whole organisms.54,55 Similar effects have been observed in human volunteers.56,57 In normal individuals, light reduces the production of melatonin. Evidence indicates that patients with bipolar disorder have increased sensitivity to light and thus melatonin inhibition, and that lithium seems to counter the melatonin-suppressing effects of light.58 Interestingly, valproate has been found to have similar activity against the suppression of melatonin production by light.59 Therefore, the mood-stabilizing effects of lithium and valproate can at least partially be attributed to their ability to counter-balance the inhibition of melatonin production by light.
For many patients with bipolar disorder, manic episodes have seasonal patterns with peaks occurring in spring or summer. Therefore, adding a seasonal mania specifier for the diagnosis of some patients with bipolar disorder may help alert clinicians so that they can better understand, predict, and manage manic symptoms as early as possible. Prospective studies are needed to evaluate the effectiveness of adjusting mood stabilizers, lifestyle, and psychotherapy according to the seasonal patterns of mania to prevent or reduce relapse at peak seasons.
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